Researchers have precisely tracked for the first time how molecular marks on DNA proteins change during cell division – and disproved a long cherished assumption in the process.
DNA does not float freely in the cell. Instead, it is wrapped around histone proteins to form structures called nucleosomes. These histones carry numerous chemical modifications that act as molecular signals, controlling how tightly the DNA is packaged and which genes are active. During cell division, this DNA-histone complex – known as chromatin – must be further condensed into compact, rod-shaped chromosomes. Histone modifications play a key role in this process: they change significantly during condensation and regulate the conversion of chromatin.
An international research team led by Professor Axel Imhof at LMU’s Biomedical Center and Professor William Earnshaw (University of Edinburgh) has analyzed these changes during cell division with unprecedented precision. To this end, the researchers developed an innovative method that synchronizes the division of cell populations. They then employed high-resolution mass spectrometry to precisely record the changes in histone modifications during cell division.
Three different phosphorylation programs
Their results show that certain chemical changes do not occur randomly, but follow a clear temporal sequence. Histone phosphorylation – the attachment of phosphate groups to histones – proceeds in three distinct programs. It begins with H3S10 phosphorylation, which rapidly spreads across nearly the entire chromatin and reaches near-complete enrichment. This is followed by transient H3T3 phosphorylation, which appears later and occurs primarily in densely packed, gene-poor regions of the genome. Finally, H3S28 phosphorylation follows its own distinct temporal pattern.
Previous assumption disproved
Furthermore, the results refute a widely held assumption. The removal of certain chemical groups from histones was long thought to be a crucial step in DNA compaction. In the cells examined in this study, no such effect was observed. Instead, the level of the corresponding modification remained largely constant – a clear indication, according to the authors, that earlier findings were artifacts of the experimental conditions used in previous studies.
“Our study provides the most precise and comprehensive picture to date of how histone modifications are orchestrated during mitosis,” says Imhof. “Many processes follow an exact temporal pattern. At the same time, we have to reconsider some previous assumptions. The histone code during mitosis is far more finely tuned and coordinated than we thought.”
Molecular Cell
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23-Apr-2026